One of the most central and discriminating processes in all living cells is achieved by specific interaction between DNA and protein. Many cellular regulations depend upon the accuracy of such specific interactions. However at present we know very little about the detailed mechanism of such interactions at atomic or structural level. None of the following questions are answered: Is there conformational change in protein and/or DNA when it recognizes specific sequence of DNA? How does this enzyme discriminate a specific sequence against a similar DNA sequence? Is there a third element, such as water molecules or metal ions, anions, etc., that participates in the specific recognition process? One of the simplest systems in which specific interactions between DNA and protein can be studied is the DNA restriction and modification system. The overall objective of this proposal is to determine 3-dimensional structures Of EcoRI restriction endonuclease and methylase, as well as their complexes with DNA of particular sequence by X-ray diffraction methods. The comparison between the 3-dimensional structures of enzymes alone and the complex between enzymes and DNA is likely to provide the answers to the questions above.